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Ann Rheum Dis 2007;66:1276-1283 doi:10.1136/ard.2006.058644
  • Extended report

Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies

  1. Sevim Barbasso Helmers1,
  2. Maryam Dastmalchi1,
  3. Helene Alexanderson2,
  4. Inger Nennesmo3,
  5. Mona Esbjörnsson4,
  6. Björn Lindvall5,
  7. Ingrid E Lundberg1
  1. 1
    Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
  2. 2
    Rheumatology Unit, Department of Medicine, Department of Physical Therapy, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
  3. 3
    Department of Pathology, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm, Sweden
  4. 4
    Division of Clinical Physiology, Department of Medical Laboratory Medicine, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm, Sweden
  5. 5
    Neuromuscular Unit, Division of Neurology, Department of Clinical Neurosciences and Locomotion, University Hospital, Linköping; Muscular Centre, Department of Neurology, University Hospital, Örebro, Sweden
  1. Sevim Barbasso Helmers, Karolinska University Hospital, Rheumatology Unit, CMM L8:04, SE-171 76 Stockholm, Sweden; Sevim.Barbasso{at}ki.se
  • Accepted 13 January 2007
  • Published Online First 2 February 2007

Abstract

Objectives: The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (IVIG) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) patients.

Methods: Thirteen treatment-resistant patients, 6 PM, 4 DM, 2 IBM and 1 juvenile DM, were treated with 2 g/kg of IVIG, three times at monthly intervals. Functional Index in Myositis and serum creatinine kinase (CK) levels were determined, and muscle biopsies were performed before treatment and after the third IVIG infusion. Immunological molecules were also studied in biopsies taken 24–48 h after the first infusion.

Results: Improved muscle function was observed in three patients (1 PM, 1 DM and 1 IBM) and CK levels decreased in five. T cells, macrophages, major histocompatibility complex (MHC) class I antigen on muscle fibres, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and membranolytic attack complex (MAC) deposits on capillaries were present to an equal degree in biopsies before and after IVIG treatment. No correlation between the clinical response and molecular changes was found.

Conclusions: The clinical effects of high-dose IVIG on muscle function in patients with refractory inflammatory active myositis did not correspond to effects on any of the investigated molecules in our study. T cells, macrophages, phenotypical changes in muscle fibres and endothelial cell activation were still present after treatment. These observations question a role for IVIG as an immune-modulating therapy in patients with inflammatory myopathies.

Footnotes

  • Competing interests: None.

  • Abbreviations:
    CD
    cluster of differentiation
    CK
    creatinine kinase
    DM
    dermatomyositis
    FI
    Functional Index in Myositis
    IBM
    inclusion body myositis
    ICAM intercellular adhesion molecule
    IL
    interleukin
    IVIG
    intravenous immunoglobulin
    MAC
    membranolytic attack complex
    MHC
    major histocompatibility complex
    PBMC
    peripheral blood mononuclear cell
    PM
    polymyositis
    VCAM
    vascular cell adhesion molecule

This Article

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    1. ard.2006.058644v1
    2. ard.2006.058644v2
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